Membrane proteins are divided into two groups based upon the ease with which the proteins can be removed from the membrane. Extrinsic or peripheral membrane proteins can be removed using extremes of ionic strength or pH, urea, or other disruptors of protein interactions. Intrinsic or integral membrane proteins are released only when the lipid bilayer of the membrane is dissolved by detergent. Extrinsic membrane proteins comprise constituents of the cytoskeleton such as spectrin and actin. Many cytoskeletal proteins are bound directly to integral membrane proteins or are bound indirectly via other proteins such as ankyrin. Cytoskeletal proteins control the shape and dynamics of the cell membrane through their interactions with motor proteins such as myosin and dynein.
The majority of known integral membrane proteins are transmembrane proteins which contain an extracellular, a transmembrane, and an intracellular domain. Transmembrane proteins are typically embedded into the cell membrane by one or more regions. These regions contain 15 to 25 hydrophobic amino acids and are predicted to adopt an .alpha.-helical conformation. Singer (1990; Annu. Rev. Cell Biol. 6:247-96) classifies these transmembrane proteins as bitopic and polytopic. Bitopic proteins (Types I and II) span the membrane once while polytopic proteins (Types III and IV) contain multiple membrane-spanning segments. A small number of monotopic, integral membrane proteins are partially embedded in the membrane and do not span the lipid bilayer. Monotopic proteins may be inserted into the bilayer by a hydrophobic hairpin loop or attached to the membrane via bound lipid.
Type II integral membrane proteins have a single transmembrane stretch of hydrophobic residues which is often located near the amino-terminus. The bulk of the type II molecule is carboxy-terminal of the hydrophobic domain. The amino-terminal domain is located on the cytoplasmic side of the membrane and is typically small. Type II proteins generally lack enzymatically active, cytoplasmic domains and are not directly involved in transmembrane signaling. The carboxy-terminal domain is the active portion of the protein and usually functions as the binding domain of a receptor.
Recently, a multigene family encoding II integral membrane proteins, the E25 gene family, was identified. The best characterized member of this family is the mouse Itm2 gene which encodes E25AMM. The Itm2 gene was expressed in osteogenic tissue in association with chondro-osteogenic differentiation. In particular, Itm2 is strongly expressed in mature osteoblasts and in early stages of secondary chondrogenesis. Itm2 was also weakly expressed in heart, brain (choroid plexus), renal cortex, and the crypts of the small intestine and strongly expressed in skin (stratum corneum), hair follicles and the acini of exocrine glands. Additional members of the E25 multigene family have been identified in the mouse and in humans where they are expressed in a wide variety of tissues including adult and fetal brain and heart, fetal liver, fetal spleen, lung, breast, placenta, prostate, adrenal gland, and white blood cells (Deleersnijder W et al. (1996) J. Biol. Chem. 271:19475).
The discovery of a new human integral membrane protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of cancer and neuronal and immunological disorders.